The overall goal of this project is to determine whether chronic pretreatment with different but defined classes of the newer antiarrhythmic compounds influence the nature and frequency of ventricular arrhythmias following coronary occlusion in the closed-chest conscious dog, and whether the effects of these agents on arrhythmias can be correlated with their electrophysiologic actions on the ischemic myocardium in relation to their serum and tissue levels. The arrhythmias will be recorded continously by Holter tapes which will be analyzed by a semiautomated method; the electrophysiological characteristics of the myocardium will be evaluated using intracellular microelectrode techniques and gas liquid chromatographic or radioimmunoassay techniquues will be used to determine the serum and tissue concentrations of different antiarrhythmic agents. The results of the project are likely to be relevant to the question of prophylactic drug administration for the reduction of the incidence of sudden death by control of ventricular arrhythmias in patients with known ischemic heart disease.